CN113350313A - Espressol omeprazole magnesium sustained-release preparation and preparation method thereof - Google Patents
Espressol omeprazole magnesium sustained-release preparation and preparation method thereof Download PDFInfo
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- CN113350313A CN113350313A CN202110697003.5A CN202110697003A CN113350313A CN 113350313 A CN113350313 A CN 113350313A CN 202110697003 A CN202110697003 A CN 202110697003A CN 113350313 A CN113350313 A CN 113350313A
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- esomeprazole magnesium
- esomeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4891—Coated capsules; Multilayered drug free capsule shells
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of medicines, in particular to an esomeprazole magnesium sustained-release preparation and a preparation method thereof.
Description
Technical Field
The invention relates to the technical field of medicines, and in particular relates to an esomeprazole magnesium sustained-release preparation and a preparation method thereof.
Background
Esomeprazole magnesium is a proton pump inhibitor that inhibits gastric acid secretion by specifically inhibiting the H +/K + -atpase of parietal cells. Currently, asilican sells esomeprazole magnesium under the trade name nexitum. Until now, the esomeprazole magnesium has various dosage forms which can be selected, such as capsules, tablets and the like. The instability of esomeprazole magnesium in acidic media necessitates the preparation of extended release formulations of the drug. Extended release delayed release formulations generally avoid the release of esomeprazole magnesium in the gastric medium and allow the drug to be released in the intestine. According to the patent of the company asikang, a Nexium (magnesium esomeprazole) extended release capsule is a hard capsule enteric pellet.
To date, all products on the market are hard capsule enteric pellets. Such as patent grant publication No. CN104606146B, patent publication No. CN1134667A, require multiple coatings on sucrose pellet cores to prepare the final enteric pellets. Coating sucrose cores multiple times is a time consuming and laborious process. The manufacturing steps included coating 3 or more coats of sucrose pellets using a fluid bed granulator/coater. Moreover, this process is cumbersome. Therefore, a preparation which is simple in preparation process, can resist gastric acid and is stable for a long time is needed.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: it is urgently needed to provide an esomeprazole magnesium preparation which is simple in preparation process, can resist gastric acid and is stable for a long time and a preparation method thereof.
In order to solve the technical problems, the invention adopts the technical scheme that:
a preparation method of an esomeprazole magnesium sustained-release preparation comprises the following steps:
step 1: producing esomeprazole magnesium pellets or granules;
step 2: filling esomeprazole magnesium pellets or granules into hydroxypropyl methyl cellulose capsules;
and step 3: coating the hydroxypropyl methyl cellulose capsules filled with the esomeprazole magnesium pellets or granules in a coating pan to prepare the esomeprazole magnesium sustained-release preparation.
The invention has the beneficial effects that: according to the preparation method of the esomeprazole magnesium sustained-release preparation, the esomeprazole magnesium pellets or granules are prepared, the esomeprazole magnesium pellets or granules are filled in the hydroxypropyl methyl cellulose capsules, and then coating is carried out.
Detailed Description
In order to explain the technical content, the objects and the effects of the present invention in detail, the following description will be given with reference to the embodiments.
The invention relates to a preparation method of an esomeprazole magnesium sustained-release preparation, which comprises the following steps:
step 1: producing esomeprazole magnesium pellets or granules;
step 2: filling esomeprazole magnesium pellets or granules into hydroxypropyl methyl cellulose capsules;
and step 3: coating the hydroxypropyl methyl cellulose capsules filled with the esomeprazole magnesium pellets or granules in a coating pan to prepare the esomeprazole magnesium sustained-release preparation.
In the preparation method of the esomeprazole magnesium sustained-release preparation, the esomeprazole magnesium pellets or granules are prepared, the esomeprazole magnesium pellets or granules are filled in hydroxypropyl methyl cellulose capsules, and then coating is carried out, compared with the traditional esomeprazole magnesium sustained-release preparation, a series of complicated steps such as preparation of a medicine suspension, coating of a medicine layer on a sucrose pill core, preparation of a barrier layer suspension, coating of a protective/barrier layer, preparation of an enteric layer dispersion liquid, coating of an enteric layer and the like are omitted, a shear barrier protective layer is not needed, multiple times of pellet coating are avoided, time and cost can be saved, sealing steps are eliminated, and medicine stability can be improved.
In the above process, esomeprazole magnesium granules/pellets are prepared so that they can flow to fill the capsules. The granules can be prepared using any available technique, such as high shear granulation, dry granulation. Extrusion spheronization may be a preferred process to obtain the spherical size advantage of the particles.
The above preparation method will be evaluated in terms of enteric properties of the coated capsules, applicability to other polymers, reproducibility of the method, release of the coated capsules, stability of the capsules, and the like.
Further, in the above preparation method of the esomeprazole magnesium extended release preparation, the step 1 specifically comprises: mixing esomeprazole magnesium with adjuvants, sieving, granulating by wet granulating machine, extrusion spheronizer, high shear granulating machine or dry granulating machine, sieving, and drying to obtain esomeprazole magnesium pellet or granule.
Further, in the above preparation method of the esomeprazole magnesium extended release preparation, the auxiliary materials include a solubilizer, a stabilizer, a binder and a solvent.
Further, in the above preparation method of the esomeprazole magnesium extended release preparation, the step 1 specifically comprises: mixing 40% esomeprazole magnesium, 5% polysorbate 80, 30% magnesium carbonate and 5% hydroxypropyl cellulose, sieving, adding 20% purified water, granulating by a high shear granulator, sieving, and drying to obtain esomeprazole magnesium granule.
Further, in the above preparation method of the esomeprazole magnesium extended release preparation, the step 1 specifically comprises: mixing 40% esomeprazole magnesium, 5% polysorbate 80, 30% magnesium carbonate, 1% sodium lauryl sulfate and 4% hydroxypropyl cellulose, sieving, adding 20% purified water, granulating with a high shear granulator, sieving, and drying to obtain esomeprazole magnesium pellet.
Further, in the preparation method of the esomeprazole magnesium sustained-release preparation, in the step 2, the water content of the hydroxypropyl methyl cellulose capsule is 4% -8%.
Further, in the above preparation method of the esomeprazole magnesium extended release preparation, the step 3 specifically comprises: and sequentially carrying out enteric coating and film coating on the hydroxypropyl methyl cellulose capsules filled with the esomeprazole magnesium pellets or granules in a coating pot to prepare the esomeprazole magnesium sustained-release preparation.
Furthermore, in the preparation method of the esomeprazole magnesium sustained-release preparation, the enteric coating adopts
FS 30D、
L30D-55、
as-HF or
Example 1
A preparation method of an esomeprazole magnesium sustained-release preparation comprises the following steps:
step 1: mixing 40% esomeprazole magnesium, 5% polysorbate 80, 30% magnesium carbonate, 1% sodium lauryl sulfate and 4% hydroxypropyl cellulose, sieving, adding 20% purified water, granulating with a high shear granulator, sieving, and drying to obtain esomeprazole magnesium pellet.
Step 2: filling the esomeprazole magnesium pellets into 3# hydroxypropyl methyl cellulose capsules; the hydroxypropyl methylcellulose capsules had a water content of 4%.
And step 3: sequentially carrying out enteric coating and film coating on the 3# hydroxypropyl methyl cellulose capsules filled with the esomeprazole magnesium pellets in a coating pot to prepare the esomeprazole magnesium sustained-release preparation. The enteric coating adopts
FS 30D。
The specific raw material amounts for the above preparation method are shown in table 1.
TABLE 1
Dissolution test conditions: basket method, 100 rpm, dissolution medium for the first two hours is 300ml of hydrochloric acid solution with pH1.2, and dissolution medium for the second two hours is 700ml of phosphate buffer solution with pH 6.8. The dissolution test results are shown in table 2 below.
TABLE 2
From the above table, it can be seen that the dissolution medium of the first two hours is 300ml of hydrochloric acid solution with ph1.2, which simulates the gastric environment, and the dissolution medium of the second two hours is 700ml of phosphate buffer solution with ph6.8, which simulates the intestinal environment, and from the above data, the esomeprazole magnesium sustained-release preparation obtained in example 1 has good stability in the gastric environment and excellent sustained-release enteric solubility in the intestinal environment.
Example 2
A preparation method of an esomeprazole magnesium sustained-release preparation comprises the following steps:
step 1: mixing 40% esomeprazole magnesium, 5% polysorbate 80, 30% magnesium carbonate and 5% hydroxypropyl cellulose, sieving, adding 20% purified water, granulating by a high shear granulator, sieving, and drying to obtain esomeprazole magnesium granule.
Step 2: filling the esomeprazole magnesium granules into 3# hydroxypropyl methyl cellulose capsules; the hydroxypropyl methylcellulose capsules had a water content of 8%.
And step 3: and sequentially carrying out enteric coating and film coating on the 3# hydroxypropyl methyl cellulose capsules filled with the esomeprazole magnesium granules in a coating pot to prepare the esomeprazole magnesium sustained-release preparation. The sausageThe dissolution coating adopts
L30D-55。
The specific raw material amounts for the above preparation method are shown in table 3.
TABLE 3
The enteric-coated capsules can be selected, and the stability, gastric juice resistance and the like of the enteric-coated capsules are evaluated before use.
Dissolution test conditions: basket method, 100 rpm, dissolution medium for the first two hours is 300ml of hydrochloric acid solution with pH1.2, and dissolution medium for the second two hours is 700ml of phosphate buffer solution with pH 6.8. The dissolution test results are shown in table 4 below.
TABLE 4
From the above table, it can be seen that the dissolution medium of the first two hours is 300ml of hydrochloric acid solution with ph1.2, which simulates the gastric environment, and the dissolution medium of the second two hours is 700ml of phosphate buffer solution with ph6.8, which simulates the intestinal environment, and from the above data, the esomeprazole magnesium sustained-release preparation obtained in example 2 has good stability in the gastric environment and excellent sustained-release enteric solubility in the intestinal environment.
In summary, in the preparation method of the esomeprazole magnesium sustained-release preparation provided by the invention, the esomeprazole magnesium pellets or granules are prepared, the esomeprazole magnesium pellets or granules are filled in the hydroxypropyl methylcellulose capsules, and then coating is carried out, compared with the traditional esomeprazole magnesium sustained-release preparation, a series of complicated steps such as preparation of a drug suspension, coating of a drug layer on a sucrose pill core, preparation of a barrier layer suspension, coating of a protective/barrier layer, preparation of an enteric layer dispersion liquid, coating of an enteric layer and the like are omitted, a shear barrier protective layer is not needed, multiple times of pellet coating can be avoided, time and cost can be saved, a sealing step can be eliminated, and the drug stability can be improved.
The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all equivalent modifications made by the present invention in the specification or directly or indirectly applied to the related technical field are included in the scope of the present invention.
Claims (10)
1. The preparation method of the esomeprazole magnesium sustained-release preparation is characterized by comprising the following steps:
step 1: producing esomeprazole magnesium pellets or granules;
step 2: filling the esomeprazole magnesium pellets or granules into 3# hydroxypropyl methyl cellulose capsules;
and step 3: and coating the 3# hydroxypropyl methyl cellulose capsules filled with the esomeprazole magnesium pellets or granules in a coating pan.
2. The method for preparing the extended release formulation of esomeprazole magnesium according to claim 1, wherein the step 1 specifically comprises: mixing esomeprazole magnesium with adjuvants, sieving, granulating by wet granulating machine, extrusion spheronizer, high shear granulating machine or dry granulating machine, sieving, and drying to obtain esomeprazole magnesium pellet or granule.
3. The process for preparing extended release formulation of esomeprazole magnesium according to claim 2, wherein the excipients comprise solubilizer, stabilizer, binder and solvent.
4. The method for preparing the extended release formulation of esomeprazole magnesium according to claim 1, wherein the step 1 specifically comprises: mixing 40% esomeprazole magnesium, 5% polysorbate 80, 30% magnesium carbonate and 5% hydroxypropyl cellulose, sieving, adding 20% purified water, granulating by a high shear granulator, sieving, and drying to obtain esomeprazole magnesium granule.
5. The method for preparing the extended release formulation of esomeprazole magnesium according to claim 1, wherein the step 1 specifically comprises: mixing 40% esomeprazole magnesium, 5% polysorbate 80, 30% magnesium carbonate, 1% sodium lauryl sulfate and 4% hydroxypropyl cellulose, sieving, adding 20% purified water, granulating with a high shear granulator, sieving, and drying to obtain esomeprazole magnesium pellet.
6. The process for preparing extended release formulation of esomeprazole magnesium according to claim 1, wherein the water content of the hydroxypropylmethylcellulose capsule in the step 2 is 4% -8%.
7. The method for preparing the extended release formulation of esomeprazole magnesium according to claim 1, wherein the step 3 specifically comprises: and sequentially carrying out enteric coating and film coating on the 3# hydroxypropyl methyl cellulose capsules filled with the esomeprazole magnesium pellets or granules in a coating pot to prepare the esomeprazole magnesium sustained-release preparation.
8. The process for preparing extended release formulation of esomeprazole magnesium according to claim 7, wherein said enteric coating employs
FS 30D、
L30D-55、
as-HF or
9. The extended release magnesium esomeprazole formulation prepared by the process for preparing the extended release magnesium esomeprazole formulation according to any one of claims 1 to 8.
10. The extended release formulation of esomeprazole magnesium according to claim 9, wherein the content of the magnesium esomeprazole contained in each granule capsule finally prepared is 20mg or 40 mg.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5690960A (en) * | 1993-07-09 | 1997-11-25 | Astra Aktiebolag | Pharmaceutical formulation of omeprazole |
| CN110585164A (en) * | 2019-10-08 | 2019-12-20 | 苏州弘森药业股份有限公司 | Method for preparing esomeprazole magnesium sodium bicarbonate capsule |
| CN110721172A (en) * | 2019-11-29 | 2020-01-24 | 江西杏林白马药业有限公司 | Espressol omeprazole magnesium enteric-coated micro-tablets and preparation method thereof |
| CN112022829A (en) * | 2019-06-04 | 2020-12-04 | 厦门恩成制药有限公司 | Method for preparing esomeprazole magnesium sodium bicarbonate capsule |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112190564A (en) * | 2020-09-27 | 2021-01-08 | 北京诺康达医药科技股份有限公司 | Compound pellet preparation and preparation method thereof |
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2021
- 2021-06-23 CN CN202110697003.5A patent/CN113350313B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5690960A (en) * | 1993-07-09 | 1997-11-25 | Astra Aktiebolag | Pharmaceutical formulation of omeprazole |
| CN112022829A (en) * | 2019-06-04 | 2020-12-04 | 厦门恩成制药有限公司 | Method for preparing esomeprazole magnesium sodium bicarbonate capsule |
| CN110585164A (en) * | 2019-10-08 | 2019-12-20 | 苏州弘森药业股份有限公司 | Method for preparing esomeprazole magnesium sodium bicarbonate capsule |
| CN110721172A (en) * | 2019-11-29 | 2020-01-24 | 江西杏林白马药业有限公司 | Espressol omeprazole magnesium enteric-coated micro-tablets and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 李汉蕴 等: "《药物制剂包衣原理工艺及设备》", 30 April 2007, 中国医药科技出版社 * |
| 陈海建等: "艾司奥美拉唑镁肠溶微丸型片剂的制备", 《中国药剂学杂志(网络版)》 * |
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